IL-2 promotes the growth and survival of CD4+ T cells, but also plays an essential role in limiting pathogenic T cell responses and maintaining self-tolerance. How this cytokine exerts these important and opposite effects on the immune system remains incompletely understood. We have recently defined a c-myc-dependent growth pathway that is induced by IL-2. This growth pathway is required for T cell proliferation and survival and our preliminary results indicate that it functions to promote T cell responses to foreign antigen in vivo and to maintain self-tolerance. In this grant we propose to 1) improve our knowledge of the components of the IL-2-induced MYC-dependent growth pathway, 2) define the role of this growth pathway in T cell responses, and 3) define the role of this growth pathway in T cell tolerance. Through these studies we hope to improve our understanding of the molecular basis by which IL-2 regulates immune responses to pathogens and acts to limit autoimmune responses and inflammatory bowel disease. [unreadable] [unreadable] [unreadable] [unreadable]